Pain management with stimulation subthreshold to paresthesia

ABSTRACT

Devices, systems and methods are provided for treating pain while minimizing or eliminating possible complications and undesired side effects, particularly the sensation of paresthesia. This is achieved by stimulating in proximity to a dorsal root ganglion with stimulation energy in a manner that will affect pain sensations without generating substantial sensations of paresthesia. In some embodiments, such neurostimulation takes advantage of anatomical features and functions particular to the dorsal root ganglion.

CROSS-REFERENCES TO RELATED APPLICATION

This application claims priority under 35 U.S.C. 119(e) to U.S.Provisional Patent Application No. 61/163,007, entitled “Pain Managementwith Subthreshold Stimulation”, filed Mar. 24, 2009, which isincorporated herein by reference.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH OR DEVELOPMENT

Not Applicable

REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAMLISTING APPENDIX SUBMITTED ON A COMPACT DISK

Not Applicable

BACKGROUND OF THE INVENTION

For more than 30 years, spinal cord stimulation (SCS) has been used totreat a variety of pain syndromes. The goal of SCS is to createparesthesia that completely and consistently covers the painful areas,yet does not cause uncomfortable sensations in other areas. Paresthesiamay be defined as a sensation of tingling, pricking, or numbness in anarea of the body. It is more generally known as the feeling of “pins andneedles”. In some instances, the feeling of paresthesia is preferredover the feeling of pain. In SCS, paresthesia production is accomplishedby stimulating Aβ fibers in the dorsal column and/or the dorsal roots.Dorsal column stimulation typically causes paresthesia in severaldermatomes at and below the level of the stimulator. In contrast, dorsalroot stimulation activates fibers in a limited number of rootlets inclose proximity to the stimulator and causes paresthesia in only a fewdermatomes. Because of these factors, dorsal root stimulation with anSCS stimulator may not produce sufficient pain relief. In addition,stimulation of the roots with an SCS stimulator can cause uncomfortablesensations and motor responses. These side effects may occur at pulseamplitudes that are below the value needed for full paresthesiacoverage. Therefore, the clinical goal of SCS is to produce anelectrical field that stimulates the relevant spinal cord structureswithout stimulating the nearby nerve root.

Intraspinal nerve root stimulation is a technique related to SCS, exceptthat electrodes are placed along the nerve rootlets in the lateralaspect of the spinal canal (this area is known as “the gutter”), ratherthan over the midline of the spinal cord. The electrodes are mounted ona cylindrical lead rather than on a traditional SCS paddle lead. Theaccuracy of the leads' placement within the gutter is confirmed bystimulating the nerve roots at perceptible levels, which result inparesthesia in the local area. Sensory paresthesia may be generated bystimulating at a level above the threshold for sensory recruitment. Thismay be used in conjunction with SCS to treat certain pain conditions.

For some patients, paresthesia is an undesired effect and is not a welltolerated alternative to pain. Therefore, improved treatments are neededto provide pain relief with minimal undesired effects. At least some ofthese objectives will be met by the present invention.

BRIEF SUMMARY OF THE INVENTION

The present invention provides devices, systems and methods for treatingconditions, such as pain, while minimizing or eliminating possiblecomplications and undesired side effects. In particular, the devices,systems and methods treat pain without generating substantial sensationsof paresthesia. This is achieved by stimulating in proximity to a dorsalroot ganglion with specific stimulation energy levels, as will bedescribed in more detail herein.

In a first aspect of the present invention, a method is provided oftreating pain in a patient comprising positioning a lead having at leastone electrode disposed thereon so that at least one of the at least oneelectrode is in proximity to a dorsal root ganglion, and providingstimulation energy to the at least one of the at least one electrode soas to stimulate at least a portion of the dorsal root ganglion. Togetherthe positioning of the lead step and the providing stimulation energystep affect pain sensations without generating substantial sensations ofparesthesia.

In some embodiments, providing stimulation energy comprises providingstimulation energy at a level below a threshold for Aβ fiberrecruitment. And, in some embodiments, providing stimulation energycomprises providing stimulation energy at a level below a threshold forAβ fiber cell body recruitment.

In other embodiments, providing stimulation energy comprises: a)providing stimulation energy at a level above a threshold for Aδ fibercell body recruitment, b) providing stimulation energy at a level abovea threshold for C fiber cell body recruitment, c) providing stimulationenergy at a level above a threshold for small myelenated fiber cell bodyrecruitment, or d) providing stimulation energy at a level above athreshold for unmyelenated fiber cell body recruitment.

In still other embodiments, providing stimulation energy comprisesproviding stimulation energy at a level which is capable of modulatingglial cell function within the dorsal root ganglion. For example, insome embodiments, providing stimulation energy comprises providingstimulation energy at a level which is capable of modulating satellitecell function within the dorsal root ganglion. In other embodiments,providing stimulation energy comprises providing stimulation energy at alevel which is capable of modulating Schwann cell function within thedorsal root ganglion.

In yet other embodiments, providing stimulation energy comprisesproviding stimulation energy at a level which is capable of causing atleast one blood vessel associated with the dorsal root ganglion torelease an agent or send a cell signal which affects a neuron or glialcell within the dorsal root ganglion.

In some embodiments, positioning the lead comprises advancing the leadthrough an epidural space so that at least a portion of the lead extendsalong a nerve root sleeve angulation. And, in some instances advancingthe lead through the epidural space comprises advancing the lead in anantegrade direction.

In a second aspect of the present invention, a method is provided fortreating a patient comprising selectively stimulating a small fiber cellbody within a dorsal root ganglion of the patient while excluding an Aβfiber cell body with the dorsal root ganglion of the patient. In someembodiments, the small fiber body comprises an Aδ fiber cell body. Inother embodiments, the small fiber body comprises a C fiber cell body.

In a third aspect of the present invention, a method is provided fortreating a patient comprising identifying a dorsal root ganglionassociated with a sensation of pain by the patient, and neuromodulatingat least one glial cell within the dorsal root ganglion so as to reducethe sensation of pain by the patient. In some embodiments, the at leastone glial cell comprises a satellite cell. In other embodiments, the atleast one glial cell comprises a Schwann cell. And, in some embodiments,neuromodulating comprises providing stimulation at a level that reducesthe sensation of pain without generating substantial sensations ofparesthesia.

In a fourth aspect of the present invention, a method is provided fortreating a patient comprising positioning a lead having at least oneelectrode disposed thereon so that at least one of the at least oneelectrode is in proximity to a dorsal root ganglion, and providingstimulation energy to the at least one electrode so as to stimulate atleast one blood vessel associated with the dorsal root ganglion in amanner that causes the at least one blood vessel to release an agentwhich neuromodulates a neuron within the dorsal root ganglion. In someembodiments, the agent comprises a neuromodulatory chemical that affectsthe function of neurons involved in pain sensory transduction.

In a fifth aspect of the present invention, a system is provided fortreating pain in a patient comprising a lead having at least oneelectrode disposed thereon, wherein the lead is configured for placementin proximity to a dorsal root ganglion, and a pulse generator configuredto provide stimulation energy to the at least one of the at least oneelectrode while the lead is positioned in proximity to the dorsal rootganglion so as to stimulate at least a portion of the dorsal rootganglion in a manner which affects pain sensations without generatingsubstantial sensations of paresthesia.

In some embodiments, the pulse generator provides stimulation energy ata level at below a threshold for Aβ fiber recruitment. In otherembodiments, the pulse generator provides stimulation energy at a levelbelow a threshold for Aβ fiber cell body recruitment. In otherembodiments, the pulse generator provides stimulation energy at a levelabove a threshold for Aδ fiber cell body recruitment. In still otherembodiments, the pulse generator provides stimulation energy at a levelabove a threshold for C fiber cell body recruitment. In someembodiments, the pulse generator provides stimulation energy at a levelabove a threshold for small myelenated fiber cell body recruitment. And,in some embodiments, the pulse generator provides stimulation energy ata level above a threshold for unmyelenated fiber cell body recruitment.

In some embodiments, the pulse generator provides stimulation energy ata level which is capable of modulating glial cell function within thedorsal root ganglion. For example, in some embodiments, the pulsegenerator provides stimulation energy at a level which is capable ofmodulating satellite cell function within the dorsal root ganglion. Inother embodiments, the pulse generator provides stimulation energy at alevel which is capable of modulating Schwann cell function within thedorsal root ganglion.

In some instances, the pulse generator provides stimulation energy at alevel which is capable of causing at least one blood vessel associatedwith the dorsal root ganglion to release an agent or send a cell signalwhich affects a neuron or glial cell within the dorsal root ganglion.

And, in some embodiments, the lead is configured to be advanced in anantegrade direction through an epidural space and positioned so that atleast a portion of the lead extends along a nerve root sleeveangulation.

Other objects and advantages of the present invention will becomeapparent from the detailed description to follow, together with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A provides a schematic illustration of a spinal cord, associatednerve roots and a peripheral nerve on a spinal level and FIG. 1Billustrates cells within a DRG.

FIGS. 2A-2C provide a cross-sectional histological illustration of aspinal cord and a DRG under varying levels of magnification.

FIG. 3 illustrates an embodiment of a lead, having at least oneelectrode thereon, advanced through the patient anatomy so that at leastone of the electrodes is positioned on a target DRG.

FIG. 4 provides a schematic illustration of the lead positioned on aDRG.

FIG. 5 illustrates a graph showing an example relationship betweenthreshold stimulus and nerve fiber diameter.

FIG. 6 illustrates recruitment order based on nerve fiber diameter.

FIG. 7 illustrates recruitment order based on cell body size.

FIG. 8 illustrates recruitment order differences based on location ofstimulation.

FIG. 9 provides a schematic illustration of an embodiment of the leadpositioned on a DRG, including various cells and anatomical structuresassociated with the DRG.

FIGS. 10A-10D, 11, 12 illustrate embodiments of a lead and deliverysystem.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides devices, systems and methods for treatingpain while minimizing or eliminating possible complications andundesired side effects, particularly the sensation of paresthesia. Thisis achieved by stimulating in proximity to a dorsal root ganglion withstimulation energy in a manner that will affect pain sensations withoutgenerating substantial sensations of paresthesia. In some embodiments,such neurostimulation takes advantage of anatomical features andfunctions particular to the dorsal root ganglion, as will be describedin more detail below. The devices, systems and methods are minimallyinvasive, therefore reducing possible complications resulting from theimplantation procedure, and targeted so as to manage pain sensationswith minimal or no perceptions such as paresthesia.

FIG. 1A provides a schematic illustration of a spinal cord S, associatednerve roots and a peripheral nerve on a spinal level. Here, the nerveroots include a dorsal root DR and a ventral root VR that join togetherat the peripheral nerve PN. The dorsal root DR includes a dorsal rootganglion DRG, as shown. The DRG is comprised of a variety of cells,including large neurons, small neurons and non-neuronal cells. Eachneuron in the DRG is comprised of a bipolar or quasi-unipolar cellhaving a soma (the bulbous end of the neuron which contains the cellnucleus) and two axons. The word soma is Greek, meaning “body”; the somaof a neuron is often called the “cell body”. Somas are gathered withinthe DRG, rather than the dorsal root, and the associated axons extendtherefrom into the dorsal root and toward the peripheral nervous system.FIG. 1B provides an expanded illustration of cells located in the DRG,including a small soma SM, a large soma SM′ and non-neuronal cells (inthis instance, satellite cells SC). FIGS. 2A-2C provide across-sectional histological illustration of a spinal cord S andassociated nerve roots, including a DRG. FIG. 2A illustrates the anatomyunder 40× magnification and indicates the size relationship of the DRGto the surrounding anatomy. FIG. 2B illustrates the anatomy of FIG. 2Aunder 100× magnification. Here, the differing structure of the DRG isbecoming visible. FIG. 2C illustrates the anatomy of FIG. 2A under 400×magnification focusing on the DRG. As shown, the larger soma SM′ and thesmaller somas SM are located within the DRG.

In some embodiments, stimulation of a DRG according to the presentinvention is achieved with the use of a lead having at least oneelectrode thereon. The lead is advanced through the patient anatomy sothat the at least one electrode is positioned on, near, about or inproximity to the target DRG. The lead and electrode(s) are sized andconfigured so that the electrode(s) are able to minimize or excludeundesired stimulation of other anatomies.

FIG. 3 illustrates an embodiment of a lead 100, having at least oneelectrode 102 thereon, advanced through the patient anatomy so that atleast one of the electrodes 102 is positioned on a target DRG. In thisexample, the lead 100 is inserted epidurally and advanced in anantegrade direction along the spinal cord S. As shown, each DRG isdisposed along a dorsal root DR and typically resides at least partiallybetween the pedicles PD or within a foramen. Each dorsal root DR exitsthe spinal cord S at an angle θ. This angle θ is considered the nerveroot sleeve angulation and varies slightly by patient and by locationalong the spinal column. However, the average nerve root angulation issignificantly less than 90 degrees and typically less than 45 degrees.Therefore, advancement of the lead 100 toward the target DRG in thismanner involves making a sharp turn along the angle θ. A turn of thisseverity is achieved with the use of delivery tools and design featuresspecific to such lead placement which will be described in more detailin later sections. In addition, the spatial relationship between thenerve roots, DRGs and surrounding structures are significantlyinfluenced by degenerative changes, particularly in the lumbar spine.Thus, patients may have nerve root angulations which differ from thenormal anatomy, such as having even smaller angulations necessitatingeven tighter turns. The delivery tools and devices accommodate theseanatomies.

FIG. 4 provides a schematic illustration of an embodiment of the lead100 positioned on a DRG. As illustrated, the DRG includes smaller somasSM and larger somas SM′. Each soma is connected with an associated axonor nerve fiber which extends through the root. The axon or nerve fiberis a long, slender projection of a nerve cell, or neuron that conductselectrical impulses away from the neuron's cell body or soma. Thesmaller somas SM have smaller axons AX and the larger somas SM′ havelarger axons AX′. Typically, axons or nerve fibers are recruitedelectrically according to size. Referring to FIG. 5, a graph is providedwhich illustrates an example relationship between threshold stimulus andnerve fiber diameter. Generally, as the nerve fiber diameter increases,the threshold stimulus decreases. Thus, as illustrated in FIG. 6, largermylenated fibers (Aβ fibers) are recruited before smaller mylenatedfibers (Aδ fibers), which are in turn recruited before small unmylenatedfibers (C fibers).

Referring to FIG. 7, the opposite is true of cell bodies compared tonerve fibers. Generally, it takes less current to recruit or modulate asmaller cell body or soma membrane than a larger one. Thus, as shown inFIG. 8, when low stimulation is provided in region A (to the cell bodiesSM′, SM) the smaller diameter cell bodies SM are selectively stimulatedbefore the larger diameter cell bodies SM′. This is due to therelatively smaller charge it takes to effectively modulate membranefunction of a smaller cell body. However, when low stimulation isprovided in region B (to the axons AX′, AX) the larger axons AX′ arestimulated before the smaller axons AX. Referring back to FIG. 4, sincethe cell bodies or somas are located within the DRG, region A generallycorresponds to the DRG and region B generally corresponds to the dorsalroot DR.

When a patient experiences pain, the nociceptive or painful stimuli aretransduced from peripheral structures to the central nervous systemsthrough small diameter, thinly myelinated and unmyelinated afferentnerve fibers or axons AX. Electrically, these fibers are more difficultto selectively target since larger diameter fibers or axons AX′ arepreferentially activated by electrical currents based upon the abovedescribed size principle. These larger fibers AX′ are associated withsensory stimuli such as light touch, pressure and vibration and well asparesthesia such as generated by SCS.

The present invention provides methods and devices for preferentiallyneuromodulating the smaller diameter axon/smaller soma neurons over thelarger diameter axon/larger soma neurons. This in turn interrupts paintransmission while minimizing or eliminating paresthesia. Referringagain to FIG. 4, an example is illustrated of a lead 100 positioned sothat at least one of the electrodes 102 is disposed so as to selectivelystimulate the DRG while minimizing or excluding undesired stimulation ofother anatomies, such as portions of the dorsal root DR. This allows thesmaller diameter axon/smaller soma neurons to be recruited before thelarger diameter axon/larger soma neurons. Consequently, these neuronsinvolved in pain transduction can be modulated without producingparesthesias. This is achieved with the use of less current or lowerpower stimulation, i.e. stimulation at a subthreshold level toparesthesia. The effect of this preferential, targeted neuromodulationis analgesia without resultant paresthesias. In addition, lower powerstimulation means lower power consumption and longer battery life.

Conventional spinal stimulation systems typically provide stimulationwith a frequency of about 30-120 Hz. In contrast, therapeutic benefitshave been achieved with the devices and methods described herein atstimulation frequencies below those used in conventional stimulationsystems. In one aspect, the stimulation frequency used for the DRGstimulation methods described herein is less than 25 Hz. In otheraspects, the stimulation frequency could be even lower such as in therange of less than 15 Hz. In still other aspects, the stimulationfrequency is below 10 Hz. In one specific embodiment, the stimulationfrequency is 5 Hz. In another specific, embodiment, the stimulationfrequency is 2 Hz. In addition to lower stimulation frequencies, otherstimulation patterns for the inventive devices and methods are alsolower than those used in conventional stimulation systems. For example,embodiments of the present invention have achieved repeatable dermatomespecific pain relief using a stimulation signal having an amplitude ofless than 500 microamps, a pulse width of less than 120 microseconds anda low stimulation frequency as discussed above. It is believed thatembodiments of the present invention can achieve dermatome specific painrelief using signals having pulse widths selected within the range of 60microseconds to 120 microseconds. It is believed that embodiments of thepresent invention can achieve dermatome specific pain relief using asignal having an amplitude of about 200 microamps. In one specificexample, repeatable dermatome specific pain relief was achieved in anadult female using a signal with an amplitude of 200 microamps, a pulsewidth of 60 microseconds and a frequency of 2 Hz. It may also beappreciated that other suitable stimulation signal parameters may beused along, such as provided in U.S. patent application Ser. No.12/607,009 entitled “Selective Stimulation Systems and Signal ParametersFor Medical Conditions”, filed Oct. 27, 2009, incorporated herein byreference for all purposes.

In addition to neuronal cells, non-neuronal cells, such as glial cells,are located within the DRG. Glial cells surround neurons, hold them inplace, provide nutrients, help maintain homeostasis, provide electricalinsulation, destroy pathogens, regulate neuronal repair and the removaldead neurons, and participate in signal transmission in the nervoussystem. In addition, glial cells help in guiding the construction of thenervous system and control the chemical and ionic environment of theneurons. Glial cells also play a role in the development and maintenanceof dysfunction in chronic pain conditions. A variety of specific typesof glial cells are found within the DRG, such as satellite cells andSchwann cells.

Satellite cells surround neuron cell bodies within the DRG. They supplynutrients to the surrounding neurons and also have some structuralfunction. Satellite cells also act as protective, cushioning cells. Inaddition, satellite cells can form gap junctions with neurons in theDRG. As opposed to classical chemical transmission in the nervoussystem, gap junctions between cells provide a direct electricalcoupling. This, in turn, can produce a form of a quasi glial-neuronalsyncytium. Pathophysiologic conditions can change the relationshipbetween glia and cell bodies such that the neurons transductinginformation about pain can become dysfunctional. Thereforeneurostimulation of the DRG can not only directly affect neurons butalso impact the function of glial cells. Modulation of glial cellfunction with neurostimulation can in turn alter neuronal functioning.Such modulation can occur at levels below a threshold for generatingsensations of paresthesia.

FIG. 9 provides a schematic illustration of an embodiment of the lead100 positioned on a DRG. As illustrated, the DRG includes satellitecells SC surrounding smaller somas SM and larger somas SM′. In someembodiments, stimulation energy provided by at least one of theelectrodes 102 neuromodulates satellite cells SC. Such neuromodulationimpacts their function and, secondarily, impacts the function ofassociated neurons so as to interrupt or alter processing of sensoryinformation, such as pain. Consequently, DRG satellite cellneuromodulation can be a treatment for chronic pain.

Another type of glial cells are Schwann cells. Also referred to asneurolemnocytes, Schwann cells assist in neuronal survival. Inmyelinated axons, Schwann cells form the myelin sheath. The vertebratenervous system relies on the myelin sheath for insulation and as amethod of decreasing membrane capacitance in the axon. The arrangementof the Schwann cells allows for saltatory conduction which greatlyincreases speed of conduction and saves energy. Non-myelinating Schwanncells are involved in maintenance of axons. Schwann cells also provideaxon support, trophic actions and other support activities to neuronswithin the DRG.

Referring again to FIG. 9, Schwann cells SWC are illustrated along theaxons of a neuron within the DRG. In some embodiments, stimulationenergy provided by at least one of the electrodes 102 of the lead 100neuromodulates Schwann cells SWC. Such neuromodulation impacts theirfunction and, secondarily, impacts the function of associated neurons.Neuromodulation of Schwann cells impacts neuronal processing,transduction and transfer of sensory information including pain. Thus,DRG stimulation relieves pain in the short and long term by impactingfunction of Schwann cells. This also may be achieved at stimulationlevels below a threshold for generating sensations of paresthesia.

Beyond the neural cells (neurons, glia, etc) that are present in theDRG, there is a rich network of blood vessels that travel in and aboutthe DRG to encapsulate the DRG and provide a blood supply and oxygen tothis highly metabolically active neural structure. FIG. 9 schematicallyillustrates a blood vessel BV associated with and an example DRG. Insome embodiments, stimulation energy is provided by at least one of theelectrodes 102 of the lead 100. Stimulation of the DRG can cause therelease of a variety of agents from the neurons, glia and/or bloodvessels which ultimately impact the function of neurons involved in thetransduction and processing of sensory information, including pain. Forexample, in some embodiments stimulation of the DRG causes one or moretypes of neurons and/or one or more types of glial cells to releasevasoactive agents which affect at least one blood vessel. The at leastone blood vessel in turn releases neuronal agents impact the function ofneurons in processing pain. Or, the at least one blood vessel releasesglial active agents which indirectly impacts the function of neurons inprocessing pain. In other embodiments, stimulation of the DRG directlyaffects the associated blood vessels which provide vessel to neuron cellsignaling or vessel to glial cell signaling. Such cell signalingultimately impacts neuronal function, such as by altering metabolic rateor inducing the release of neural responsive chemicals which, in turn,directly change the cell function. The change in cell function inducesanalgesia or pain relief in the short-term, mid-term and long-term. Suchchanges may occur at stimulation levels below a threshold for generatingsensations of paresthesia.

Desired positioning of a lead 100 near the target anatomy, such as theDRG, may be achieved with a variety of delivery systems, devices andmethods. Referring back to FIG. 3, an example of such positioning isillustrated. In this example, the lead 100 is inserted epidurally andadvanced in an antegrade direction along the spinal cord S. As shown,each DRG is disposed along a dorsal root DR and typically resides atleast partially between the pedicles PD or within a foramen. Each dorsalroot DR exits the spinal cord S at an angle θ. This angle θ isconsidered the nerve root sleeve angulation and varies slightly bypatient and by location along the spinal column. However, the averagenerve root angulation is significantly less than 90 degrees andtypically less than 45 degrees. Therefore, advancement of the lead 100toward the target DRG in this manner involves making a sharp turn alongthe angle θ. In addition, the spatial relationship between the nerveroots, DRGs and surrounding structures are significantly influenced bydegenerative changes, particularly in the lumbar spine. Thus, patientsmay have nerve root angulations which differ from the normal anatomy,such as having even smaller angulations necessitating even tighterturns. Turns of this severity are achieved with the use of deliverytools having design features specific to such lead placement.

Referring to FIGS. 10A-10D, an example lead and delivery devices foraccessing a target DRG are illustrated. FIG. 10A illustrates anembodiment of a lead 100 comprising a shaft 103 having a distal end 101with four electrodes 102 disposed thereon. It may be appreciated thatany number of electrodes 102 may be present, including one, two, three,four, five, six, seven, eight or more. In this embodiment, the distalend 101 has a closed-end distal tip 106. The distal tip 106 may have avariety of shapes including a rounded shape, such as a ball shape(shown) or tear drop shape, and a cone shape, to name a few. Theseshapes provide an atraumatic tip for the lead 100 as well as servingother purposes. The lead 100 also includes a stylet lumen 104 whichextends toward the closed-end distal tip 106. A delivery system 120 isalso illustrated, including a sheath 122 (FIG. 10B), stylet 124 (FIG.10C) and introducing needle 126 (FIG. 10D).

Referring to FIG. 10B, an embodiment of a sheath 122 is illustrated. Inthis embodiment, the sheath 122 has a distal end 128 which is pre-curvedto have an angle α, wherein the angle α is in the range of approximately80 to 165 degrees. The sheath 122 is sized and configured to be advancedover the shaft 103 of the lead 100 until a portion of its distal end 128abuts the distal tip 106 of the lead 100, as illustrated in FIG. 11.Thus, the ball shaped tip 106 of this embodiment also prevents thesheath 122 from extending thereover. Passage of the sheath 122 over thelead 100 causes the lead 100 to bend in accordance with the precurvatureof the sheath 122. Thus, the sheath 122 assists in steering the lead 100along the spinal column S and toward a target DRG, such as in a lateraldirection.

Referring back to FIG. 10C, an embodiment of a stylet 124 isillustrated. The stylet 124 has a distal end 130 which is pre-curved sothat its radius of curvature is in the range of approximately 0.1 to0.5. The stylet 124 is sized and configured to be advanced within thestylet lumen 104 of the lead 100. Typically the stylet 124 extendstherethrough so that its distal end 130 aligns with the distal end 101of the lead 100. Passage of the stylet 124 through the lead 100 causesthe lead 100 to bend in accordance with the precurvature of the stylet124. Typically, the stylet 124 has a smaller radius of curvature, or atighter bend, than the sheath 122. Therefore, as shown in FIG. 12, whenthe stylet 124 is disposed within the lead 100, extension of the lead100 and stylet 124 through the sheath 122 bends or directs the lead 100through a first curvature 123. Further extension of the lead 100 andstylet 124 beyond the distal end 128 of the sheath 122 allows the lead100 to bend further along a second curvature 125. This allows thelaterally directed lead 100 to now curve around toward the target DRGalong the nerve root angulation. This two step curvature allows the lead100 to be successfully positioned so that at least one of the electrodes102 is on, near or about the target DRG, particularly by making a sharpturn along the angle θ.

Thus, the lead 100 does not require stiff or torqueable constructionsince the lead 100 is not torqued or steered by itself. The lead 100 ispositioned with the use of the sheath 122 and stylet 124 which directthe lead 100 through the two step curvature. This eliminates the needfor the operator to torque the lead 100 and optionally the sheath 122with multiple hands. This also allows the lead 100 to have a lowerprofile as well as a very soft and flexible construction. This, in turn,minimizes erosion and discomfort created by pressure on nerve tissue,such as the target DRG and/or the nerve root, once the lead 100 isimplanted. For example, such a soft and flexible lead 100 will minimizethe amount of force translated to the lead 100 by body movement (e.g.flexion, extension, torsion).

Referring back to FIG. 10D, an embodiment of an introducing needle 126is illustrated. The introducing needle 126 is used to access theepidural space of the spinal cord S. The needle 126 has a hollow shaft127 and typically has a very slightly curved distal end 132. The shaft127 is sized to allow passage of the lead 100, sheath 122 and stylet 124therethrough. In some embodiments, the needle 126 is 14 gauge which isconsistent with the size of epidural needles used to place conventionalpercutaneous leads within the epidural space. However, it may beappreciated that other sized needles may also be used, particularlysmaller needles such as 16-18 gauge. Likewise, it may be appreciatedthat needles having various tips known to practitioners or custom tipsdesigned for specific applications may also be used. The needle 126 alsotypically includes a Luer-Lok™ fitting 134 or other fitting near itsproximal end. The Luer-Lok™ fitting 134 is a female fitting having atabbed hub which engages threads in a sleeve on a male fitting, such asa syringe.

Methods of approaching a target DRG using such a delivery system 120 isfurther described and illustrated in U.S. Patent Application No.61/144,690 filed Jan. 14, 2009, incorporated herein by reference for allpurposes, along with examples of other delivery systems, devices andmethods applicable to use with the present invention.

It may be appreciated that other types of leads and correspondingdelivery systems may be used to position such leads in desiredorientations to provide stimulation subthreshold to paresthesia. Forexample, the lead may have a pre-curved shape wherein the lead isdeliverable through a sheath having a straighter shape, such as asubstantially straight shape or a curved shape which is has a largerradius of curvature than the lead. Advancement of the lead out of thesheath allows the lead to recoil toward its pre-curved shape. Variouscombinations of curvature between the lead and sheath may allow for avariety of primary and secondary curvatures. Once the lead is desirablyplaced, the sheath may then be removed.

It may also be appreciated that a variety of approaches to the DRG maybe used, such as an antegrade epidural approach, a retrograde epiduralapproach, a transforamenal approach or an extraforaminal approach(approaching along a peripheral nerve from outside of the spinalcolumn), and a contralateral approach, to name a few. Likewise, the atleast one electrode may be positioned in, on or about, in proximity to,near or in the vicinity of the DRG.

Although the foregoing invention has been described in some detail byway of illustration and example, for purposes of clarity ofunderstanding, it will be obvious that various alternatives,modifications, and equivalents may be used and the above descriptionshould not be taken as limiting in scope of the invention which isdefined by the appended claims.

1. A method of treating pain in a patient comprising: positioning a leadhaving at least one electrode disposed thereon so that at least one ofthe at least one electrode is in proximity to a dorsal root ganglion;and providing stimulation energy to the at least one of the at least oneelectrode so as to stimulate at least a portion of the dorsal rootganglion, wherein together the positioning of the lead step and theproviding stimulation energy step reduce pain sensations withoutgenerating sensations of paresthesia.
 2. A method as in claim 1, whereinproviding stimulation energy comprises providing stimulation energy at alevel below a threshold for Aβ fiber recruitment.
 3. A method as inclaim 2, wherein providing stimulation energy comprises providingstimulation energy at a level below a threshold for Aβ fiber cell bodyrecruitment.
 4. A method as in claim 3, wherein providing stimulationenergy comprises providing stimulation energy at a level above athreshold for M fiber cell body modulation.
 5. A method as in claim 3,wherein providing stimulation energy comprises providing stimulationenergy at a level above a threshold for C fiber cell body modulation. 6.A method as in claim 3, wherein providing stimulation energy comprisesproviding stimulation energy at a level above a threshold for smallmyelenated fiber cell body modulation.
 7. A method as in claim 3,wherein providing stimulation energy comprises providing stimulationenergy at a level above a threshold for unmyelenated fiber cell bodymodulation.
 8. A method as in claim 1, wherein providing stimulationenergy comprises providing stimulation energy at a level which iscapable of modulating glial cell function within the dorsal rootganglion.
 9. A method as in claim 8, wherein providing stimulationenergy comprises providing stimulation energy at a level which iscapable of modulating satellite cell function within the dorsal rootganglion.
 10. A method as in claim 8, wherein providing stimulationenergy comprises providing stimulation energy at a level which iscapable of modulating Schwann cell function within the dorsal rootganglion.
 11. A method as in claim 1, wherein providing stimulationenergy comprises providing stimulation energy at a level which iscapable of causing at least one blood vessel associated with the dorsalroot ganglion to release an agent or send a cell signal which affects aneuron or glial cell within the dorsal root ganglion.
 12. A method as inclaim 1, wherein positioning the lead comprises advancing the leadthrough an epidural space so that at least a portion of the lead extendsalong a nerve root sleeve angulation.
 13. A method as in claim 12,wherein advancing the lead through the epidural space comprisesadvancing the lead in an antegrade direction.
 14. A method of treating apatient comprising: selectively electrically stimulating a small fibercell body within a dorsal root ganglion of the patient while excludingan Aβ fiber cell body within the dorsal root ganglion of the patient.15. A method as in claim 14, wherein the small fiber body comprises a Mfiber cell body.
 16. A method as in claim 14, wherein the small fiberbody comprises a C fiber cell body.
 17. A method of treating a patientcomprising: identifying a dorsal root ganglion associated with asensation of pain by the patient; and electrically neuromodulating atleast one glial cell within the dorsal root ganglion so as to reduce thesensation of pain by the patient.
 18. A method as in claim 17, whereinthe at least one glial cell comprises a satellite cell.
 19. A method asin claim 17, wherein the at least one glial cell comprises a Schwanncell.
 20. A method as in claim 17, wherein neuromodulating comprisesproviding stimulation at a level that reduces the sensation of painwithout generating substantial sensations of paresthesia.
 21. A methodof treating a patient comprising: positioning a lead having at least oneelectrode disposed thereon so that at least one of the at least oneelectrode is in proximity to a dorsal root ganglion; and providingstimulation energy to the at least one electrode so as to stimulate atleast one blood vessel associated with the dorsal root ganglion in amanner that causes the at least one blood vessel to release an agentwhich neuromodulates a neuron within the dorsal root ganglion.
 22. Amethod as in claim 21, wherein the agent comprises a neuromodulatorychemical that affects the function of neurons involved in pain sensorytransduction.